Overview of knowledge, attitudes and barriers associated with HPV vaccination in Beirut, Lebanon.

BACKGROUND: Human Papillomavirus (HPV), a prevalent sexually transmitted infection carrying significant risks ranging from benign lesions to various types of malignancies, represents a matter of great public health concern. Notably, most Arab countries lack public awareness campaigns or national immunization programs. This study aims at assessing the overall knowledge on HPV and HPV vaccination among the Lebanese population, exploring the prevalent attitude on the matter, and identifying barriers and misconceptions that prevent individuals from receiving the HPV vaccine. METHODS: A cross-sectional study was conducted in Beirut, on 201 participants aged between 18 and 36 years old. We performed ordinal analysis to assess the trend between Knowledge levels, attitude levels and hesitancy Levels. RESULTS: Majority of participants (77%) demonstrated a low level of knowledge on HPV vaccination, 50% held a positive attitude, with only 18.4% being already vaccinated. Negative trend was identified between levels of knowledge, attitude and hesitancy (gamma = -0.7415, p-value < 0.01; gamma= -0.58, p-value < 0.01 respectively). Unavailability or limited access to the vaccine, and misconceptions about HPV immunization were shown to be impeding vaccination. CONCLUSION: Analysis of our results strongly suggests that improving knowledge and attitudes is likely to foster trust and reduce hesitancy, thereby promoting higher vaccine uptake.

Comparing the 30-Day Complications Between Smokers and Nonsmokers Undergoing Surgical Fixation of Ankle Fractures.

Background: There have been conflicting reports regarding the effect of smoking on complications after surgical treatment of ankle fractures. This study aimed at identifying the complications for which smokers and subgroups of smokers are at a higher risk compared to nonsmokers when undergoing surgery for fixation of rotational ankle fractures. Methods: The American College of Surgeons National Surgical Quality Improvement Program data set from 2008 to 2019 was used to compare the 30-day wound, cardiac, renal, and infectious complications, related readmissions, and return to the operating room between the 2 cohorts. Results: Of 33 741 patients included, 25 642 (76.0%) were nonsmokers and 8099 (24.0%) were smokers. Multivariate analysis showed that smokers were at a higher risk for deep wound infection (OR 2.34, 95% CI 1.48-3.69, P < .001), wound dehiscence (OR 2.43, 95% CI 1.56-3.77, P < .001), related return to the operating room (OR 1.69, 95% CI 1.36-2.11, P < .001), and related readmissions (OR 1.67, 95% CI 1.32-2.09, P < .001). Smokers at an increased risk for deep infection included patients between 50 and 59 years (OR 5.75, 95% CI 1.78-18.5, P = .003), who were Black (OR 4.24, 95% CI 1.04-17.23, P = .044), who had body mass index (BMI) 35 to 39.9 (OR 3.73, 95% CI 1.46-9.50, P = .006), or operative times between 60 and 90 minutes (OR 3.64, 95% CI 1.79-7.39, P < .001). Smoker subgroups at a higher risk for wound dehiscence included patients between 50 and 59 years (OR 9.86, 95% CI 3.29-29.53, P < .001), with operative times between 90 and 120 minutes (OR 4.88, 95% CI 1.89-12.58, P < .001), with BMI 30 to 34.9 (OR 3.06, 95% CI 1.45-6.45, P = .003) and who underwent spinal/epidural anesthesia (OR 9.31, 95% CI 2.31-37.58, P = .002). Conclusion: Smokers were at an increased risk for deep wound infection, wound dehiscence, related reoperations, and related readmissions after ankle fracture surgery. Certain subgroups were at an even higher risk for these complications. Level of Evidence: Level III, retrospective cohort study.

Is breast conservation superior to mastectomy in early stage triple negative breast cancer?

PURPOSE: Compare overall survival (OS) and breast cancer-specific survival (BCSS) outcomes of breast conservative therapy (BCT) and mastectomy in a large cohort of patients with early-stage triple negative breast cancer (TNBC), using a propensity score-based matching approach. METHODS: Surveillance, Epidemiology, and End Results (SEER) database was used to study the role of RT in early stage TNBC. Primary end points were OS and BCSS. Cox proportional hazard regression models and Kaplan-Meier plots were used to generate the desired outcomes. Propensity score matching was done to minimize bias. RESULTS: 12,761 patients with T1-2N0M0 TNBC as their first malignancy were retrieved. Of these 7237 had lumpectomy with RT, and 5524 had mastectomy only. Age, race, marital status, tumor laterality, grade and stage, and receipt of chemotherapy were prognostic variables for OS and BCSS. Among 4848 matched subjects, the 5-year OS was significantly higher in patients with lumpectomy and RT (89%) compared to mastectomy alone (84.5%) (p-value <0.001). Similarly, BCSS was significantly higher in patients with lumpectomy and RT (93%) compared to mastectomy alone (91%) (p-value <0.001). On subgroup analysis, patients who are younger than 40 had similar survival outcomes after either mastectomy alone or lumpectomy with RT. However, those who are older than 60, have any grade or T stage had better survival outcomes with lumpectomy and RT. CONCLUSIONS: Overall, lumpectomy followed by RT is associated with better OS and BCSS compared to mastectomy in T1-2N0M0 TNBC patients. Further research is needed to determine the optimal treatment strategy for specific patient subgroups.

Application of a novel microscopic technique for quantifying CA125 binding to circulating mononuclear cells in longitudinal specimens during treatment for ovarian cancer.

BACKGROUND: Measurement of serum CA125, an antigenic fragment of human mucin 16 (MUC16), is used to monitor the clinical progression of epithelial ovarian cancer (EOC). However, rather than simply a passive marker reflecting tumor burden, MUC16 may have a more active role by binding to immune cells and altering their tumor response. We developed a research tool to measure MUC16-binding to the surfaces of peripheral blood mononuclear cell (PBMC) subtypes and tested its research value using specimens collected serially from a woman being treated for high grade serous EOC. METHODS: Cryopreserved PBMCs were mixed with anti-CA125 antibody-labeled plasmonic gold nanoparticles (PNPs) to detect cell surface MUC16-binding along with fluorescent stains to identify B cells, NK cells, NK-T cells, T cells, and monocytes. From 3D darkfield images, a computer algorithm was applied to enumerate PNP-binding and fluorescence microscopy to identify cell lineage. Average MUC16-binding was determined by fitting a Poisson distribution to PNP-counts across similar cell types. MUC16-binding to cell types was correlated with treatment details, CA125 levels, and complete blood count (CBC) data. RESULTS: Over a 21-month period, monocytes had the highest level of MUC16-binding which was positively correlated with serum CA125 and inversely correlated with circulating monocyte and lymphocyte counts. Fluctuations of PNP-binding to NK cells were associated temporally with types of chemotherapy and surgical events. Levels of MUC16 bound to NK cells were positively correlated with levels of MUC16 bound to T and NK-T cells and inversely correlated with circulating platelets. CONCLUSIONS: Assessment of MUC16-binding among cryopreserved PBMC cell types can be accomplished using darkfield and fluorescence microscopy. Correlations observed between level of binding by cell type with serum CA125, CBC data, and treatment details suggest that the new techniques may offer novel insights into EOC's clinical course.

Characterization of Cell-Bound CA125 on Immune Cell Subtypes of Ovarian Cancer Patients Using a Novel Imaging Platform.

MUC16, a sialomucin that contains the ovarian cancer biomarker CA125, binds at low abundance to leucocytes via the immune receptor, Siglec-9. Conventional fluorescence-based imaging techniques lack the sensitivity to assess this low-abundance event, prompting us to develop a novel "digital" optical cytometry technique for qualitative and quantitative assessment of CA125 binding to peripheral blood mononuclear cells (PBMC). Plasmonic nanoparticle labeled detection antibody allows assessment of CA125 at the near-single molecule level when bound to specific immune cell lineages that are simultaneously identified using multiparameter fluorescence imaging. Image analysis and deep learning were used to quantify CA125 per each cell lineage. PBMC from treatment naïve ovarian cancer patients (N = 14) showed higher cell surface abundance of CA125 on the aggregate PBMC population as well as on NK (p = 0.013), T (p < 0.001) and B cells (p = 0.024) compared to circulating lymphocytes of healthy donors (N = 7). Differences in CA125 binding to monocytes or NK-T cells between the two cohorts were not significant. There was no correlation between the PBMC-bound and serum levels of CA125, suggesting that these two compartments are not in stoichiometric equilibrium. Understanding where and how subset-specific cell-bound surface CA125 takes place may provide guidance towards a new diagnostic biomarker in ovarian cancer.

Plasmonic Nanoparticle-Based Digital Cytometry to Quantify MUC16 Binding on the Surface of Leukocytes in Ovarian Cancer.

Although levels of the circulating ovarian cancer marker (CA125) can distinguish ovarian masses that are likely to be malignant and correlate with severity of disease, serum CA125 has not proved useful in general population screening. Recently, cell culture studies have indicated that MUC16 may bind to the Siglec-9 receptor on natural killer (NK) cells where it downregulates the cytotoxicity of NK cells, allowing ovarian cancer cells to evade immune surveillance. We present evidence that the presence of MUC16 can be locally visualized and imaged on the surface of peripheral blood mononuclear cells (PBMCs) in ovarian cancer via a novel "digital" cytometry technique that incorporates: (i) OC125 monoclonal antibody-conjugated gold nanoparticles as optical nanoprobes, (ii) a high contrast dark-field microscopy system to detect PBMC-bound gold nanoparticles, and (iii) a computational algorithm for automatic counting of these nanoparticles to estimate the quantity of surface-bound MUC16. The quantitative detection of our technique was successfully demonstrated by discriminating clones of the ovarian cancer cell line, OVCAR3, based on low, intermediate, and high expression levels of MUC16. Additionally, PBMC surface-bound MUC16 was tracked in an ovarian cancer patient over a 17 month period; the results suggest that the binding of MUC16 on the surface of immune cells may play an early indicator for recurrent metastasis 6 months before computational tomography-based clinical diagnosis. We also demonstrate that the levels of surface-bound MUC16 on PBMCs from five ovarian cancer patients were greater than those from five healthy controls.

Molecular and biophysical analysis of apoptosis using a combined quantitative phase imaging and fluorescence resonance energy transfer microscope.

Apoptotic mechanisms are often dysregulated in cancerous phenotypes. Additionally, many anticancer treatments induce apoptosis and necrosis, and the monitoring of this apoptotic activity can allow researchers to identify therapeutic efficiency. Here, we introduce a microscope which combines quantitative phase imaging (QPI) with the ability to detect molecular events via fluorescence (or Förster) resonance energy transfer (FRET). The system was applied to study cells undergoing apoptosis to correlate the onset of apoptotic enzyme activity as observed using a FRET-based apoptosis sensor with whole cell morphological changes analyzed via QPI. The QPI data showed changes in cell disorder strength during the initiation of apoptotic enzymatic activity.